Introduction and Key Concepts for the Endocrine System

The endocrine system is very closely associated with the nervous system and is much like the nervous system in some ways. The nervous system sends messages related to sensation, thought, and motor control using electrochemical signals (action potentials) that are carried by neurons and axons. The endocrine system sends messages to control and regulate the metabolic activity of the body using chemical signals (hormones) that are released by endocrine secretory cells and carried by the blood circulatory system. The endocrine system includes (1) endocrine glands, such as the pituitary gland, thyroid and parathyroid glands, adrenal glands, and the pineal gland; (2) clusters of endocrine cells located in the organs such as islets of Langerhans in the pancreas; and (3) isolated endocrine cells in certain tissues, such as the enteroendocrine cells in the epithelium of the respiratory and digestive tracts (see Chapters 11, “Respiratory System,” and 15, “Digestive Tract”). The endocrine organs that are discussed in this chapter include the pituitary gland, parathyroid glands, adrenal glands, and the endocrine pancreas (islets of Langerhans). Other endocrine organs, such as the testes and ovaries, are discussed in Chapters 18, “Male Reproductive System,” and 19, “Female Reproductive System.”

Endocrine secretions (hormones) are delivered through the capillary network of the vascular system to the target organs rather than through a series of ducts as in the exocrine system. The timing of hormone release is controlled by the hypothalamus. The hypothalamus acts as a command center, controlling the activity of the pituitary gland. The pituitary gland functions as a master gland, releasing hormones to control other endocrine glands and organs. The organs or tissues that are activated by released hormones are called target organs or tissues. The cells in the target organ/tissue have appropriate

receptors, which are able to recognize and respond to specific hormones (Fig. 17-2).

The hormones can be divided into three classes based on their structure:

1.Steroid hormones are lipid hormones that have the characteristic ring structure of steroids (terpenoid lipids) and are formed from cholesterol. Examples of these hormones include estrogen, testosterone, cortisone, and aldosterone.

2.Peptide hormones are composed of amino acids and are usually produced by the partial hydrolysis of proteins. The majority of hormones of this type are secreted by the pituitary gland (e.g., adrenocorticotropic hormone [ACTH], thyroidstimulating hormone [TSH], follicle-stimulating hormone [FSH], prolactin, and growth hormones) and parathyroid glands (parathyroid hormone [PTH], or parathormone).

3.Amine hormones are derived from the amino acid tyrosine.

Examples include triiodothyronine (T3) and thyroxine (T4) released by the thyroid and sympathomimetic hormones (adrenaline/epinephrine and noradrenaline/norepinephrine) secreted by the adrenal medulla.

Pituitary Gland

The pituitary gland is a neuroendocrine organ located inside the skull and considered a part of the brain (Figs. 17-2 to 17-6B). It consists of two divisions: the adenohypophysis (anterior lobe) and the neurohypophysis (posterior lobe). The pituitary gland produces various types of hormones that act on many target organs, many of which also secrete hormones (Fig. 17-2). Secretion of the pituitary gland is controlled and regulated by releasing hormone and inhibitory hormone secreted by the hypothalamus or by nervous system signals from the hypothalamic nuclei, including the paraventricular nuclei, the supraoptic

nuclei, and the arcuate nuclei. The hypothalamus itself receives signals from many areas of the brain, including the amygdala, hippocampus, brainstem tegmentum, and the infralimbic and cingulate cortices. The hypothalamus maintains body homoeostasis by regulating production of the hypothalamic hormones, which, in turn, control the secretion of the pituitary hormones from the pituitary gland.

THE ADENOHYPOPHYSIS, also called the anterior pituitary, is the anterior division of the gland and is derived from the ectoderm of the roof of the developing oral cavity (Rathke pouch). It is composed of glandular tissue. The adenohypophysis can be divided into three regions based on their anatomic positions: the pars distalis, pars tuberalis, and pars intermedia.

1.The pars distalis is the main body of the adenohypophysis, containing blood vessels, a capillary network, and two main types of secretory cells supported by a network of reticular connective tissues. These secretory cells are classified as chromophobes and chromophils. The chromophobes do not effectively take a stain, so they appear clear in the Mallory trichrome stain. These cells are undifferentiated cells but are capable of differentiating into chromophils. The chromophils include basophils and acidophils (Fig. 17-4A).

Basophils appear blue in Mallory stain and include three subtypes of hormone secretory cells: corticotrophs, thyrotrophs, and gonadotrophs. Various hormones are produced by these cells, including ACTH, TSH, FSH, and luteinizing hormone

(LH). These hormones stimulate various target organs including the cortex of the adrenal glands, the thyroid, the testes, and the ovaries (see Fig. 17-2 for details). The secretion of hormones by cells in the adenohypophysis is controlled by hypothalamic releasing hormones and inhibitory hormones. Corticotrophs are stimulated by corticotropin-releasing hormone (CRH) from the hypothalamus. Thyrotrophs are stimulated by thy- rotropin-releasing hormone. Gonadotrophs are stimulated by gonadotropin-releasing hormone.

Acidophils appear red in Mallory stain and contain two subtypes of hormone secretory cells: somatotrophs and mammotrophs. Somatotrophs secrete somatotropin (growth hormone), which stimulates the liver to produce the insulin-like growth factor (IGF-1) that promotes cartilage and bone growth, protein deposition, and cell reproduction. Mammotrophs secrete prolactin, which increases mammary gland size and promotes milk production.

2.The pars tuberalis is the neck of the adenohypophysis; it wraps around the infundibular stalk of the pituitary gland (Fig. 17-3A). It contains a rich capillary network and some low columnar basophilic cells that are commonly arranged in cords.

3.The pars intermedia is located between the pars distalis and pars nervosa (Figs. 17-3A and 17-5A). It contains cuboidal follicular cells and colloid cysts called Rathke cysts, which are lined by follicular cells. Rathke cysts are derived from the ectoderm of the dorsal portion of the Rathke pouch;

these cysts are considered to be the remnants of the Rathke pouch that was present during development. The secretory cells may be involved in producing melanocyte-stimulating hormone (MSH). These cells are usually lightly stained by basophilic dye.

THE NEUROHYPOPHYSIS is derived from the inferior surface of the developing diencephalon. It is considered to be nervous tissue. It can be divided into the infundibular stalk, the median eminence, and the pars nervosa.

1.The infundibular stalk connects the median eminence to the pars nervosa (Fig. 17-3A,B).

2.The median eminence connects the inferior portion of the hypothalamus to the infundibular stalk of the neurohypophysis (Fig. 17-3B). It contains long axons that carry antidiuretic hormone (ADH) and oxytocin hormone produced by nuclei in the hypothalamus. These axons pass through the median eminence and terminate in the pars nervosa. The median eminence also contains short axons and axon terminal endings from the hypothalamus that release neurosecretory hormones (hypothalamic releasing and inhibiting hormones). These hormones are transported through the hypophyseal portal system from the primary capillary plexus to the secondary capillary plexus, thereby regulating the secretion of the secretory cells in the adenohypophysis.

3.The pars nervosa is the main body of the neurohypophysis (Figs. 17-3A and 17-6A,B). It contains a fenestrated capillary plexus, pituicytes (glial cells), and axons and axon terminal endings from neuron cell bodies in the hypothalamus. Pituicytes provide support and nutrition to the axons of the neurons. The enlarged axon terminal endings are filled with neurosecretory granules that are called Herring bodies. The neurosecretory hormones released in the pars nervosa include ADH or vasopressin, oxytocin hormone, and neurophysins.

Thyroid Gland

The thyroid gland has two lobes that are located inferior to the thyroid cartilage and anterior to the trachea. It contains thyroid follicles that produce T3 and T4, which regulate body metabolism (Fig. 17-8A,B). The parafollicular cells located between the follicles are known as clear cells (C cells) and produce calcitonin hormone. This hormone is released in response to high blood calcium and inhibits the activity of the osteoclasts. Calcitonin is involved in calcium and phosphorus metabolism. It decreases blood calcium levels and has opposing effects to the parathormone or PTH.

Parathyroid Glands

There are typically four small parathyroid glands, most commonly lying posterior to the thyroid gland. They consist of chief cells and oxyphil cells (Fig. 17-9A,B). Chief cells are hormoneproducing cells that secrete parathormone, also called PTH. PTH is released in response to low blood calcium levels and indirectly promotes the proliferation and activity of osteoclasts, which remove bone. PTH also inhibits the activity of osteoblasts, which help to build up new bone.

Endocrine Organs with Figure Numbers

Pituitary glands

Figure 17-2

Figure 17-3A

Figure 17-3B

Figure 17-3C

Figure 17-4A

Figure 17-4B

Figure 17-5A

Figure 17-5B

Figure 17-6A

Figure 17-6B

Figure 17-7A–C

Thyroid glands

Figure 17-8A

Figure 17-8B

Figure 17-8C

Parathyroid glands

Figure 17-9A

Figure 17-9B

Figure 17-9C

Adrenal glands

Figure 17-10A

Figure 17-10B

Figure 17-11A

Figure 17-11B

Figure 17-12A

Figure 17-12B

Pineal glands

Figure 17-13A

Figure 17-13B

Figure 17-13C

Endocrine pancreas (islet of Langerhans)

Figure 17-14A

Figure 17-14B

Figure 17-15A

Figure 17-15B

Figure 17-16

Pituitary Gland

I.Adenohypophysis (anterior pituitary gland)

A.Pars distalis

1.Chromophobes

2.Chromophils

a.Acidophils: Somatotrophs (secrete growth hormone), mammotrophs/lactotrophs (secrete prolactin)

b.Basophils: Corticotrophs (secrete ACTH), thyrotrophs (secrete TSH), gonadotrophs (secrete FSH and LH)

B.Pars/tuberalis: Gonadotrophs (secrete FSH and LH)

C.Pars intermedia

1.Rathke cysts (colloid-containing cysts)

2.Basophilic cells/melanotrophs (secrete MSH)

II.Neurohypophysis (posterior pituitary gland)

A.Neural (infundibular) stalk

B.Median eminence

C.Pars nervosa

1.Herring bodies (contain neurosecretory granules)

2.Neurohypophyseal hormones: ADH (secreted by neurons whose cell bodies are in the supraoptic nucleus), oxytocin (secreted by neurons whose cell bodies are in both supraoptic and paraventricular nuclei)

Abbreviations

ACTH: Adrenocorticotropic hormone

TSH: Thyroid-stimulating hormone

FSH: Follicle-stimulating hormone

LH: Luteinizing hormone

MSH: Melanocyte-stimulating hormone

Pituitary

Pituitary

gland

gland

Pineal

gland Infundibular stalk

Pituitary

gland

A

Figure 17-3A. Overview of the pituitary gland.

The pituitary gland is a small, bean-shaped gland, about 1 cm in diameter, located inferior to the hypothalamus and separated from it by the diaphragma sellae through which the infundibular stalk (infundibulum) passes. The pituitary gland lies within the sella turcica. Various important surrounding structures are visible in the photograph and inset. The pituitary gland is located inferior, and slightly caudal, to the optic chiasm; this is a particularly important anatomical relationship that is applicable to clinical medicine.

A pituitary tumor, as it enlarges, may impinge on the crossing fibers within the optic chiasm, causing visual field deficits. This most commonly results in bitemporal hemianopia, a loss of the temporal visual fields of both eyes. Other visual field deficits can also result from pituitary tumors.

Capsule

Pars nervosa

Pars distalis

Figure 17-3C. Pituitary gland. Mallory trichrome and H&E, 31

The adenohypophysis (anterior pituitary gland) with its connective tissue capsule is shown on the left of the microphotograph. It stains red-blue because it contains chromophils (acidophils and basophils) and chromophobes. The pars nervosa of the neurohypophysis (posterior pituitary gland) is nervous tissue; it is shown on the right. It contains axons, pituicytes, and capillaries. It stains much lighter than the adenohypophysis. The cell bodies of these axons are located in the supraoptic and paraventricular nuclei of the hypothalamus. These neurons have long axons that extend from the hypothalamus into the neurohypophysis of the pituitary gland. The axons contain neurosecretory granules consisting of two types of hormones: oxytocin (supraoptic and paraventricular nuclei) and ADH (supraoptic nucleus). Enlarged axon terminal endings are known as Herring bodies (Fig. 17-6A,B).

Figure 17-5A. Pars intermedia, anterior pituitary gland.

Mallory trichrome and H&E, 127

The pars intermedia originates from the ectoderm of the Rathke pouch and is part of the adenohypophysis. This bandlike structure lies between the pars distalis and pars nervosa. It is of the same embryonic origin as the pars distalis. The pars intermedia contains colloid cysts called Rathke cysts, which are lined by cuboidal to columnar follicular cells. These cells are associated with the formation of MSH in the fetus. This photomicrograph shows several colloid-filled cysts (Rathke cysts). Most cells in the pars intermedia resemble basophilic cells (melanotrophs). A blood vessel separates the pars intermedia and the pars distalis.

Normal

Prolactinoma—H&E

A

Acidophils

Tumor cells

Normal

Prolactinoma—immunocytochemistry

B

Prolactin-producing

cells

Tumor cells

Figure 17-7A,B. Pituitary Adenoma. A:

H&E, (left) 213; (right) 154. B: Immunocytochemistry, (left) 213; (right) 154

Pituitary adenomas are benign tumors of the anterior pituitary gland. Clinically, they can be divided into nonsecreting and secreting forms. Historically, adenomas were classified by their staining properties, the degree to which they took up the stains hematoxylin and eosin. They were classified as basophilic, acidophilic, or chromophobic adenomas. With modern immunocytochemical techniques, however, tumor cells can be classified by the type of hormone they produce. Some cells do not mark with any antibody, and their tumors are called null-cell adenomas. Pituitary tumors may compress the hypothalamus, cranial nerves, or the optic chiasm. A bitemporal hemianopia is commonly seen in patients suffering from compression of the optic nerve. Mutations are believed to play a role in the development of the tumors. Pathologically, the tumors are composed of uniform, polygonal cells arrayed in sheets or cords. They lack a reticular network of supporting connective tissue and show monomorphism. Treatment includes drug therapy and surgery, depending on the type and the size of the tumors. A: The prolactinoma lacks acidophils and has tumor cells with pleomorphic nuclei (variable size nuclei). The normal tissue of the pars distalis of the pituitary gland shows individual or clusters of acidophils interspersed among basophils and chromophobes (right). B: The cell membranes of prolactin-producing tumor cells have been stained brown using an immunocytochemical reaction. The majority of the cells in this sample are tumor cells. By contrast, in the normal tissue sample shown on the right, only a small number of prolactin-producing cells are stained.

A

Connective

tissue septum

Follicle

Septum

Colloid

Figure 17-8A. Thyroid follicles, thyroid gland. H&E, 70

The thyroid gland is derived from the developing endoderm of the foramen cecum of the tongue; it has two lobes and is one of the largest endocrine glands. Connective tissue septa divide the thyroid gland into lobules. Each lobule consists of numerous thyroid follicles. The thyroid follicles are the main functional components of the gland; they synthesize and release T3 and T4. Each follicle is filled with colloid, which is a gelatinous substance containing the stored form of T3 and T4. The follicular cells are usually simple cuboidal cells but may change to simple squamous (inactive) or columnar cells (active) depending on their states of secretion (Fig. 17-8B).

The thyroid hormones play an important role in regulating the basal metabolic activity of the body. Iodine is required for formation of thyroxine; iodine deficiency can lead to the development of thyroid goiters (nodules).

B

Follicular (squamous) cells

Figure 17-8B. Parafollicular cells, thyroid gland. H&E, 702

Another type of endocrine cell located between the follicules of the thyroid gland is called a parafollicular cell. These cells are also called clear cells or C cells and are commonly located within the interstitial connective tissue septa. Parafollicular cells produce calcitonin, which inhibits osteoclasts from resorbing bone tissue, thereby decreasing blood calcium levels. High blood calcium levels stimulate parafollicular cells to secrete calcitonin. Parafollicular cells are relatively large cells with round nuclei and pale cytoplasm. They can be found scattered beneath the follicular cells or in small groups in the interstitial connective tissue between the follicles, as shown here.

Graves disease is an example of hyperthyroidism in which excessive amounts of thyroid hormones are secreted by follicular cells (see Fig. 3-5C). In hypothyroidism, thyroid glands produce abnormally low levels of thyroid hormones, such as in Hashimoto thyroiditis.

CLINICAL CORRELATION

Figure 17-8C. Hashimoto Thyroiditis. H&E, 55

Hashimoto thyroiditis is a chronic autoimmune disease, characterized by enlargement of the thyroid gland (goiter) and gradual failure of thyroid function. Hashimoto thyroiditis is the most common cause of hypothyroidism in the United States and primarily affects women. Autoantibodies against thyroid antigens, genetic susceptibility, and environmental factors are believed to play a role in the development of the disease. The signs and symptoms related to hypothyroidism include fatigue, increased sensitivity to cold, pale skin, constipation, muscle pain and weakness, and weight gain. Histologically, infiltrating lymphocytes form lymphoid follicles (lymphatic nodules) with germinal centers within the thyroid parenchyma. Some thyroid follicle cells show Hurthle cell change with abundant eosinophilic cytoplasm. Thyroid hormone replacement therapy is the treatment for the disease. Surgery may be indicated if enlargement of the thyroid gland causes compression of the airway.

Figure 17-9B. Chief cells and oxyphil cells of the parathyroid glands. H&E, 139; inset 296

The chief cells are smaller and more numerous than the oxyphil cells. They are distributed throughout the glands and are the principal cells in the parathyroid glands. Each chief cell has a large round nucleus with a small amount of clear cytoplasm. These chief cells produce PTH, also called parathormone, which is secreted in response to low blood calcium levels. PTH indirectly promotes osteoclast proliferation and increases their activity of absorption of bone tissue to increase blood calcium levels. The oxyphil cells are large cells with acidophilic (pink) cytoplasm as shown here. Each cell has a small nucleus and a large amount of cytoplasm containing numerous mitochondria. The oxyphil cells are often arranged in clusters; individual cells can also be found scattered among the chief cells. The oxyphil cells appear at puberty, and their numbers increase with age. Their functions are unclear.

C

Adenoma composed of chief cells

Normal parathyroid gland with adipose tissue

Adipocytes

Figure 17-9C. Parathyroid Adenoma. H&E, 96

Parathyroid adenomas are benign neoplasms of the parathyroid gland representing the most common cause of primary hyperparathyroidism, in which autonomous overproduction of parathyroid hormone occurs. The increased parathyroid hormone results in elevated blood calcium (hypercalcemia), which may cause constipation, kidney stones, neuropsychiatric issues, and bone diseases such as osteitis fibrosa cystica. The majority of cases are asymptomatic, discovered incidentally when hypercalcemia is detected on routine blood tests. Most cases are sporadic, but some cases may be related to inherited conditions like multiple endocrine neoplasia (MEN1 and MEN2). Parathyroid adenomas are usually solitary, whereas parathyroid hyperplasia tends to affect all four glands. Grossly, these adenomas are well circumscribed with a red-to-brown cut surface. Histologically, an adenoma is enveloped with a capsule, is usually composed of monomorphic chief cells, and tends to compress the surrounding normal parathyroid tissue. Definitive treatment is surgical removal of the parathyroid gland containing the adenoma.

Adrenal Glands (Suprarenal Glands)

Fig. 17-10B

A

Cortex

Medulla

Capsule

Zona reticularis

Zona fasciculata

Zona glomerulosa

Figure 17-10A. Overview of the adrenal glands. H&E, 7

An adrenal gland covers the apical region of each kidney. It is also called the suprarenal gland (Fig. 17-1A). Each adrenal gland is covered by a connective tissue capsule and has a cortex and a medulla. The cortex of the adrenal gland is derived from the mesoderm and can be divided into three zones: the zona glomerulosa, zona fasciculata, and zona reticularis. Hormone-producing cells in the cortex secrete several types of hormones: mineralocorticoids, glucocorticoids, and weak androgens. The medulla of the adrenal gland is derived from the neural crest and contains cell bodies of sympathetic ganglion neurons and their axons as well as chromaffin cells, which synthesize and release adrenaline

(epinephrine) and noradrenaline (norepinephrine) (Fig. 17-12A,B).

CLINICAL CORRELATION

B

Adjacent normal adrenal cortex

Pheochromocytoma

with zellballen

Figure 17-11B. Pheochromocytoma. H&E, ×96 Pheochromocytomas are neoplasms of the adrenal medulla characterized by the production of catecholamines, such as epinephrine and norepinephrine, which cause significant hypertension, often episodic, in affected patients. Most pheochromocytomas are sporadic, but about 10% are associated with familial syndromes such as MEN (types 2A and 2B), and von Hippel-Lindau. Some pheochromocytomas are bilateral, and although most occur in adults, about 10% occur in children. Grossly, most of these tumors are well circumscribed and range in size from a few grams to kilograms. Microscopically, pheochromocytomas can have a diverse appearance, from spindle cells to large, bizarre cells. The cells are often arranged in nests, or cell packets called zellballen. Histologic features alone do not reliably separate benign tumors from malignant ones; therefore, the demonstration of metastases is necessary to ascertain malignancy. Definitive treatment is surgical removal of the tumor.

Cell bodies of ganglion neurons

Chromaffin

cells

Nerve fibers

The adrenal medulla is derived from the neural crest; its embryonic origin is different from that of the adrenal cortex. The cells in the adrenal medulla include chromaffin cells and ganglion neurons. Large blood vessels (veins) are found in the medulla; these vessels drain blood out of the adrenal gland. Chromaffin cells are irregularly shaped neuroendocrine cells and are the predominant cells in the adrenal medulla. These cells have round nuclei with pale-staining cytoplasm as shown here. They have numerous plasma secretory granules that stain intensively with chromium salts; therefore, they are called chromaffin cells. These cells secrete the sympathomimetic hormones adrenaline (epinephrine) and noradrenaline (norepinephrine) in response to stress. The sympathetic ganglion neurons have large cell bodies that are surrounded by supporting cells as shown in the left inset. The adrenal medulla is innervated by sympathetic preganglionic nerves.

Pineal Gland

A

Capsule

Pineal

gland

Posterior commissure Superior

colliculus

Brain Septum sand

Figure 17-13A. Overview of the pineal gland. H&E, 5

The pineal gland is a pinecone-shaped neuroendocrine gland about 8 mm in length that produces melatonin and is covered by a capsule of pia mater. The pineal gland is part of the epithalamus (a diencephalic structure) that extends caudally from its attachment immediately superior to the posterior commissure into the superior (quadrigeminal) cistern. It is superior to the colliculi of the midbrain. Secretion of melatonin is stimulated by darkness and inhibited by light. The level of this hormone increases during sleep. Connective septa divide the pineal into poorly defined lobules. This gland contains pinealocytes, neuroglial cells, and blood vessels. Calcified concretions called brain sand (also called corpora arenacea) may also be present in the pineal gland, especially in older patients.

The calcifications (brain sand) within the pineal gland increase with age. These calcifications appear white in computed tomography scan and magnetic resonance imaging and are commonly used as a natural landmark by radiologists and neurologists.

Capillary

Neuroglial

cells

Neuroglial

cells Capillary

Brain sand

Brain

sand

Figure 17-13B. Pinealocytes and brain sand of the pineal gland.

H&E, 140; insets 363

The pineal gland is composed of two types of cells: pinealocytes and neuroglial cells. The pinealocytes are modified neurons, which have round or ovoid nuclei with pale-stained cytoplasm containing granules filled with melatonin. The pinealocytes synthesize melatonin, which is important in the regulation of the circadian rhythms (day and night cycles). The pinealocytes are larger than the neuroglial cells and have a long cytoplasmic process that extends to the capillaries; their secretory granules are released into the capillaries. The neuroglial cells are supportive cells with small, dark nuclei. They are also called pineal astrocytes and are commonly found near the capillaries. The particles of brain sand assume various sizes as shown here; their function is not known. Other functions of the pineal gland may relate to promoting sleep and sexual development; enhancing mood and slowing the aging process; and, possibly, inhibiting the growth of some tumors.

CLINICAL CORRELATION

C

Tumor

Nucleus of tumor cell

Synaptophysin in tumor cell cytoplasm

Figure 17-13C. Pineoblastoma. Immunohistochemical preparation for synaptophysin, 198

Pineoblastoma is an aggressive malignant tumor in children, which arises in the pineal gland. Because it commonly consists of cellular sheets that lack an architectural pattern, it is described as a small blue cell tumor. The term embryonal is also used to emphasize the rudimentary developmental stage of the tumor, although in some tumors the cells begin to show differentiation into neurons, or glial cells, or even rods and cones. The earliest stages of such specialization may be detectable before any architectural alteration. Synaptophysin is a protein associated with synapses. An antibody to this marker protein, conjugated to the enzyme peroxidase, creates a colored metabolite wherever synaptophysin appears in cell cytoplasm or membranes. In the image on the left, a brown compound marks the tumor cells that contain synaptophysin. Tumor treatments can be individually formulated based on the different cellular components.

Endocrine Pancreas

A

Connective Islets of tissue

Langerhans

Exocrine secretory cells

Figure 17-14A. Islets of Langerhans, endocrine pancreas. H&E,

39

The pancreas has endocrine and exocrine components. The endocrine component consists of the islets of Langerhans, which are clusters of endocrine cells within a capillary network. There are numerous palestaining islets of Langerhans scattered throughout the pancreas, and each of them is surrounded by an eosinophilic exocrine component of the pancreas as shown here. A connective tissue septum divides the pancreas into lobules. Two interlobular ducts, surrounded by the connective tissue, belong to the exocrine pancreas, from which they carry secretions. The endocrine pancreas does not have ducts; the hormones (insulin and glucagon) secreted by the islets of Langerhans are released into the capillaries and from there into the blood circulation. Insulin and glucagons play important roles in regulating blood glucose levels. Insulin stimulates glucose entry in many cells, thereby regulating carbohydrate metabolism and lowering blood glucose levels. Glucagon enhances the synthesis and release of glucose from the liver into the blood, thus increasing blood glucose levels.

A

Insulin-producing

(beta) cells

Exocrine

secretory Capillaries cells

Figure 17-15A. Pancreatic islet cells, islets of Langerhans.

Immunocytochemistry stain, 189

This is an example of an islet of Langerhans prepared with a special immunocytochemistry stain for insulin. Cells with brown color are insulin-producing cells and are the predominant cells in the islets of Langerhans. Insulinproducing cells, also called beta cells, are distributed throughout the pancreatic islets. The background counterstain is hematoxylin, which makes the endocrine pancreatic cells appear light blue with darker blue–stained nuclei.

Type 1 diabetes mellitus is the most common type of diabetes in childhood and adolescence (65% of total cases). It is characterized by insulin deficiency and sudden onset of severe hyperglycemia, diabetic ketoacidosis, and death if patients are left without insulin treatment. Symptoms also include polyuria, polydipsia, lethargy, and weight loss. The major cause of the disease is autoimmune destruction of the insulin-secreting beta cells in the islets of Langerhans by T cells and humoral mediators (tumor necrosis factor, interleukin-1, nitric oxide). Treatment options depend largely on patient and physician preferences and include baseline doses of insulin plus adjustable premeal doses of short-acting insulin or rapid-acting insulin analogs.

B

Secretory granules in beta cell

Endocrine secretory cell

Rough endoplasmic reticulum

Golgi complex

Secretory granules in alpha cell

Erythrocyte in lumen of fenestrated capillary

CLINICAL CORRELATION

Exocrine

pancreas

Amyloid replacing

islet of Langerhans

Figure 17-16. Type 2 Diabetes Mellitus. H&E, 195 Type 2 diabetes mellitus is characterized by hyperglycemia with normal or elevated insulin levels, in contrast to type 1 diabetes in which hyperglycemia is associated with little or no insulin production. In type 2 diabetes, insulin is present, but insulin-sensitive tissues, such as skeletal muscle and adipose tissues, manifest resistance to the action of insulin. Defects in beta cell function also contribute to the disease process. Type 2 diabetes generally has an insidious onset and typically affects adults. Risk factors include genetic factors and a strong association with obesity. Approximately 85% of type 2 diabetes is associated with obesity. Clinically, patients present primarily with polyuria and polydipsia due to the hyperglycemia. Chronic hyperglycemia leads to accelerated atherosclerosis and small vessel damage, which affects the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy). Early in the disease, the islets of Langerhans become hyperplastic in order to produce more insulin. Later in the disease, the islets become atrophic with amyloid deposition. Treatment includes diet modification and exercise to induce weight loss and the use of oral hypoglycemic medications. Some patients may require insulin late in the disease process because of progressive loss of beta cells.